Assessment of visual function in blind mice and monkeys with subretinally implanted nanowire arrays as artificial photoreceptors.

Retinal prostheses could restore image-forming vision in conditions of photoreceptor degeneration. However, contrast sensitivity and visual acuity are often insufficient. Here we report the performance, in mice and monkeys with induced photoreceptor degeneration, of subretinally implanted gold-nanoparticle-coated titania nanowire arrays providing a spatial resolution of 77.5 µm and a temporal resolution of 3.92 Hz in ex vivo retinas (as determined by patch-clamp recording of retinal ganglion cells). In blind mice, the arrays allowed for the detection of drifting gratings and flashing objects at light-intensity thresholds of 15.70-18.09 µW mm-2, and offered visual acuities of 0.3-0.4 cycles per degree, as determined by recordings of visually evoked potentials and optomotor-response tests. In monkeys, the arrays were stable for 54 weeks, allowed for the detection of a 10-µW mm-2 beam of light (0.5° in beam angle) in visually guided saccade experiments, and induced plastic changes in the primary visual cortex, as indicated by long-term in vivo calcium imaging. Nanomaterials as artificial photoreceptors may ameliorate visual deficits in patients with photoreceptor degeneration.

Exosomes Derived from M2 Microglial Cells Modulated by 1070-nm Light Improve Cognition in an Alzheimer's Disease Mouse Model.

Near-infrared photobiomodulation has been identified as a potential strategy for Alzheimer's disease (AD). However, the mechanisms underlying this therapeutic effect remain poorly characterize. Herein, it is illustrate that 1070-nm light induces the morphological alteration of microglia from an M1 to M2 phenotype that secretes exosomes, which alleviates the ß-amyloid burden to improve cognitive function by ameliorating neuroinflammation and promoting neuronal dendritic spine plasticity. The results show that 4 J cm-2 1070-nm light at a 10-Hz frequency prompts microglia with an M1 inflammatory type to switch to an M2 anti-inflammatory type. This induces secretion of M2 microglial-derived exosomes containing miR-7670-3p, which targets activating transcription factor 6 (ATF6) during endoplasmic reticulum (ER) stress. Moreover, it is found that miR-7670-3p reduces ATF6 expression to further ameliorate ER stress, thus attenuating the inflammatory response and protecting dendritic spine integrity of neurons in the cortex and hippocampus of 5xFAD mice, ultimately leading to improvements in cognitive function. This study highlights the critical role of exosomes derive from 1070-nm light-modulated microglia in treating AD mice, which may provide a theoretical basis for the treatment of AD with the use of near-infrared photobiomodulation.

Research on aerobic oxidation of methane bacteria and its influencing factors in Chongqing central city section of the Yangtze River, China.

Bacterial communities play an important role in the carbon cycle of freshwater ecosystems. In order to understand the influencing factors of bacterial community in the process of carbon cycle and search for measures to reduce carbon emissions, Chongqing central city section of the Yangtze River and its tributaries were selected to be the study area in this research. High-throughput sequencing was applied to study aerobic oxidation of methane bacteria (MOB) in sampling area. The results showed that there were spatial differences in the community diversity of aerobic MOB in the Yangtze River in central Chongqing. The Shannon index in the sediment (2.389-2.728) was higher than that in the water (1.820-2.458), and the community diversity in the middle reaches of the main river was higher than that in the upstream and the downstream. The aerobic MOB community was mainly dominated by Type II (Methylocystis). Most of operational taxonomic units (OTUs) in the top ten had high homology with MOB from river and lake sediments, and a few OTUs had high homology with MOB from paddy fields, forests and wetland soils. The main environmental factors affecting the community structure of aerobic MOB were NH4+-N, dissolved oxygen (DO), temperature (T, p ≤ 0.001), pH (p ≤ 0.05), methane (CH4) and carbon dioxide (CO2).

Investigation of exposure biomarkers in human plasma following differing levels of tobacco-specific N-nitrosamines and nicotine in cigarette smoke.

Tobacco-specific N-nitrosamines (TSNAs) are strong carcinogens widely found in tobacco products, environmental tobacco smoke, lake, and wastewater. The main objective of this study was to investigate the effects of cigarette smoke with different yields of TSNAs (NNK, NNN, NAT, NAB) and nicotine on the levels of biomarkers of exposure in smokers' plasma. Three hundred healthy volunteers were recruited comprising 60 smokers of each of 3 mg, 8 mg and 10 mg ISO tar yield cigarettes and 60 smokers who smoked 10 mg, 8 mg, and 3 mg for 14 days sequentially and 60 non-smokers. All study participants were male, aged from 21 to 45 years old, and were recruited from a same unit in Hebei, China. We measured the levels of NNAL, NAT, NNN, NAB and cotinine in plasma from 240 smokers and 60 non-smokers using a novel method established by online two-dimensional solid phase extraction-liquid chromatography-tandem mass spectrometry. The results showed that NNAL, NAT, NNN, NAB and cotinine in the plasma of smokers smoking cigarette with low TSNAs and nicotine were lower than that with high TSNAs and nicotine. When smokers switched from higher to lower TSNA yields of cigarettes, their plasma NNAL, NAT, NNN, NAB levels significantly decreased. The plasma concentrations of NNAL were significantly correlated with those of cotinine, NNN, NAT and NAB for smokers (p < 0.001). Similarly, the plasma concentrations of cotinine were significantly correlated with those of NNN, NAT and NAB for smokers (p < 0.001). The plasma NNAL, NAT, NNN, NAB and cotinine levels for smokers were significantly higher than those for non-smokers. These findings suggested that the total NNAL, NNN, NAT, NAB and cotinine in plasma were valid and reliable biomarkers for human exposure to TSNAs and nicotine.

Study on the hydrophobicity of [Bmim]2[CuCl4] by two-dimensional correlation spectroscopy.

By dissolving copper chloride in [Bmim]Cl (1-butyl-3-methylimidazolium chloride), chloride ions can coordinate with copper ions and form [CuCl4]2-, thereby inducing the solution being hydrophobic. In the present work, hydrogen bonds between [Bmim]+ and anions are analyzed and discussed by two-dimensional correlation spectroscopy. Time-dependent attenuated total reflection spectroscopy (ATR-FTIR) is introduced to monitor the hygroscopic process of [Bmim]2[CuCl4] and [Bmim]Cl in situ. Hygroscopic capacity and rate of [Bmim]2[CuCl4] shrink compared with [Bmim]Cl. The change of water molecular clusters has been studied by second-derivative spectra in the hygroscopic process. The behaviors of water molecular in the two ionic liquids are also distinctive.

The characteristics and influencing factors of dissolved methane concentrations in Chongqing's central urban area in the Three Gorges Reservoir, China.

Methane (CH4) emissions from reservoirs have received widespread attention. The central urban area of Chongqing in the Three Gorges Reservoir area was selected as the study area in 2020. The temporal and spatial distribution of dissolved CH4 concentration and flux, key generation pathways, and influencing factors have been studied. The dissolved CH4 concentration in low-water-level period and impoundment period varied from 0.037~0.12 µmol·L-1 and 0.11~0.23 µmol·L-1, with the average values of (0.066 ± 0.0067) µmol·L-1 and (0.13 ± 0.034) µmol·L-1. The CH4 flux was (0.941 ± 0.217) µmol·m-2·h-1 in low-water-level period and (1.915 ± 0.204) µmol·m-2·h-1 in impoundment period. CH4 was produced by CO2 reduction and acetic acid fermentation, accounting for 17.95% and 82.05% of the total CH4 production, respectively. The dissolved CH4 concentration was significantly positively correlated with DO and NO3--N, and it is opposite with dissolved inorganic carbon. The dissolved CH4 concentration in this study area is affected by water environment (33.42%), inorganic nitrogen (29.60%), organic carbon (23.88%), and inorganic carbon (13.10%), and anthropogenic influences promoted dissolved CH4 concentration.

Tracking Eye Movements During Sleep in Mice.

Eye movement is not only for adjusting the visual field and maintaining the stability of visual information on the retina, but also provides an external manifestation of the cognitive status of the brain. Recent studies showed similarity in eye movement patterns between wakefulness and rapid eye movement (REM) sleep, indicating that the brain status of REM sleep likely resembles that of awake status. REM sleep in humans could be divided into phasic REM and tonic REM sleep according to the difference in eye movement frequencies. Mice are the most commonly used animal model for studying neuronal and molecular mechanisms underlying sleep. However, there was a lack of details for eye movement patterns during REM sleep, hence it remains unknown whether REM sleep can be further divided into different stages in mice. Here we developed a device combining electroencephalogram (EEG), electromyogram (EMG) as well as eye movements recording in mice to study the eye movement patterns during sleep. We implanted a magnet beneath the conjunctiva of eye and tracked eye movements using a magnetic sensor. The magnetic signals showed strong correlation with video-oculography in head-fixed mice, indicating that the magnetic signals reflect the direction and magnitude of eye movement. We also found that the magnet implanted beneath the conjunctiva exhibited good biocompatibility. Finally, we examined eye movement in sleep-wake cycle, and discriminated tonic REM and phasic REM according to the frequency of eye movements, finding that compared to tonic REM, phasic REM exhibited higher oscillation power at 0.50 Hz, and lower oscillation power at 1.50-7.25 Hz and 9.50-12.00 Hz. Our device allowed to simultaneously record EEG, EMG, and eye movements during sleep and wakefulness, providing a convenient and high temporal-spatial resolution tool for studying eye movements in sleep and other researches in mice.

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-d-glucoside Restores BDNF-TrkB and FGF2-Akt Signaling Axis to Attenuate Stress-induced Depression.

Depression is a long term inhibitory mood that heavily disabled human beings. We have previously demonstrated anti-depression effect of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glucoside (THSG) in chronic-restraint stress (CRS) induced depressive-like mice by restoring the oxidative pathway and neuroinflammation. In this study, we examine the conditions of neurotrophins in CRS-induced depressive-like mice and whether THSG could be an antidepressant by ameliorating the neurotrophins and their associated signaling axis. CRS produced downregulation of antioxidants, the decline of brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2) and associated signaling regulators in the hippocampus and prefrontal cortex, corresponding to the behavioral inability and anhedonia. Administration of THSG restored the expression of antioxidants and neurotrophins BDNF, FGF2. Besides, THSG recovered the Akt signaling pathway and antagonistically restored the expression of Bcl-2 and cleaved-caspase-3 to inhibit apoptosis. Consistently, behavioral performances were recovered from CRS-induced motor inability and anhedonia. In summary, THSG is effective to attenuate stress-induced depression by ameliorating the biochemistry of neurotrophins and their related signaling pathways. These results may provide an avenue to take BDNF as a target to explore folk medicine for anti-depression.

2,3,5,4'-Tetrahydroxystilbene-2-O-beta-D-glucoside Reverses Stress-Induced Depression via Inflammatory and Oxidative Stress Pathways.

Major depressive disorder (MDD) is a chronic mental disease that adversely affects human mood and cognition. Many first-line antidepressant drugs have high rates of partial responsiveness or nonresponsiveness with side effects, and finding more effective drugs for the treatment of depression is therefore urgently needed. THSG, a main active compound of the traditional Chinese herb Polygonum multiflorum, reportedly acts as a neuroprotective agent. This study aimed to illustrate whether THSG prevents depressive-like behaviors induced by chronic restraint stress (CRS) in an MDD mouse model. Our results demonstrated that the peripheral administration of different THSG doses (10 mg/kg, 20 mg/kg, and 40 mg/kg) reversed the depressive-like behaviors in CRS mice as measured by the tail suspension test, forced swimming test, and open-field test. Further analyses suggested that THSG treatment reduced oxidative stress in both the central and peripheral nervous systems of CRS mice. In addition, heightened inflammatory responses, demonstrated by the increased expression of proinflammatory factors (TNF-α, IL-1ß, and IL-6), in hippocampal and prefrontal cortex tissues of CRS mice were inhibited by THSG administration. THSG also restored the diminished Akt signaling pathway in the brains of CRS mice. Moreover, our data suggest increased astrocyte proliferation and neurogenesis in the hippocampus of CRS mice after THSG treatment. Taken together, our results demonstrated an antidepressant effect of THSG in a mouse model of MDD for the first time, and oxidative stress and inflammatory pathways were determined to play roles in this effect.

Protective CD8+ T lymphocytes in primates immunized with malaria sporozoites.

Live attenuated malaria vaccines are more potent than the recombinant protein, bacterial or viral platform vaccines that have been tested, and an attenuated sporozoite vaccine against falciparum malaria is being developed for humans. In mice, attenuated malaria sporozoite vaccines induce CD8(+) T cells that kill parasites developing in the liver. We were curious to know if CD8(+) T cells were also important in protecting primates against malaria. We immunized 9 rhesus monkeys with radiation attenuated Plasmodium knowlesi sporozoites, and found that 5 did not develop blood stage infections after challenge with live sporozoites. We then injected 4 of these protected monkeys with cM-T807, a monoclonal antibody to the CD8 molecule which depletes T cells. The fifth monkey received equivalent doses of normal IgG. In 3 of the 4 monkeys receiving cM-T807 circulating CD8(+) T cells were profoundly depleted. When re-challenged with live sporozoites all 3 of these depleted animals developed blood stage malaria. The fourth monkey receiving cM-T807 retained many circulating CD8(+) T cells. This monkey, and the vaccinated monkey receiving normal IgG, did not develop blood stage malaria at re-challenge with live sporozoites. Animals were treated with antimalarial drugs and rested for 4 months. During this interval CD8(+) T cells re-appeared in the circulation of the depleted monkeys. When all vaccinated animals received a third challenge with live sporozoites, all 5 monkeys were once again protected and did not develop blood stage malaria infections. These data indicate that CD8(+) T cells are important effector cells protecting monkeys against malaria sporozoite infection. We believe that malaria vaccines which induce effector CD8+ T cells in humans will have the best chance of protecting against malaria.

Role of signal sequence in vaccine-induced protection against experimental coccidioidomycosis.

The vaccine efficacy of the gene sequence encoding the signal peptide of the antigen known as antigen 2 or proline-rich antigen (Ag2/PRA), an immunodominant antigen present in the cell wall of the fungal pathogen Coccidioides immitis, was investigated in a murine model of coccidioidomycosis. Expression plasmids for Ag2/PRA(1-18) DNA (signal sequence), Ag2/PRA(19-194) DNA (lacking the signal sequence), and Ag2/PRA(1-194) DNA (full length) were inserted in the pVR1012 vector, and the constructs were used to vaccinate the highly susceptible BALB/c mouse strain. Immunization with the signal gene sequence significantly reduced the fungal burden in the lungs and spleens of mice 12 days after intraperitoneal challenge with a lethal dose of 2,500 C. immitis arthroconidia, to a level comparable to the protection induced in mice immunized with the full-length Ag2/PRA(1-194) DNA. The Ag2/PRA(19-194) gene protected mice but to a significantly lower level than the signal sequence or the full-length Ag2 gene. The immunizing capacity of Ag2/PRA(1-18) was not attributable to a nonspecific immunostimulatory effect of DNA, as evidenced by the fact that mice immunized with a frameshift mutation of Ag2/PRA(1-18) were not protected against challenge. Furthermore, a synthetic peptide corresponding to the translated sequence of Ag2/PRA(1-18) DNA protected mice, albeit at a lower level than the Ag2/PRA(1-18) DNA vaccine. The protection induced with the signal gene vaccine correlated with the production of gamma interferon when splenocytes from Ag2/PRA(1-18)-immunized mice were stimulated with recombinant full-length Ag2 and was not associated with the production of anti-Coccidioides immunoglobulin G antibody. This is the first study to establish that a signal peptide sequence alone, administered as a gene vaccine or synthetic peptide, can induce protective immunity against a microbial pathogen.